Zoárd Tibor Krasznai

Selective Advantage of NACT in Advanced Ovarian Cancer: A Retrospective Single-Centre Analysis

Background and Objectives: Advanced-stage epithelial ovarian cancer (EOC) is associated with poor prognosis, with complete macroscopic cytoreduction representing the strongest modifiable predictor of survival. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is an alternative to primary debulking surgery (PDS) in patients with high tumor burden. However, its impact on surgical complexity remains debated. This study aimed to compare operative characteristics and survival outcomes between NACT + IDS and PDS using standardized scoring metrics in a real-world oncologic setting. Materials and Methods: We retrospectively analyzed 47 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV high-grade serous EOC treated between January 2018 and August 2022 at a single tertiary center. Twenty-five patients received platinum–taxane-based NACT followed by IDS, and twenty-two underwent upfront PDS with adjuvant chemotherapy. Surgical effort was quantified using the Surgical Complexity Score (SCS), and intra-abdominal tumor burden was assessed via the Peritoneal Cancer Index (PCI). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier analysis. Hazard ratios (HRs) with 95% confidence intervals were derived from Cox proportional hazards models. Results: Complete cytoreduction (R0) was achieved in 76% of the NACT + IDS group and 68% of the PDS group. Mean surgical complexity and operative time were significantly lower following NACT (SCS 5.0 vs. 6.2, p = 0.04; 140 vs. 197 min, p = 0.001), without significant differences in blood loss, complication rates, or length of hospital stay. Median PFS was 25 months in the NACT + IDS group versus 21 months in the PDS group, and the difference was not statistically significant. Among patients with R0 resection, survival outcomes were comparable between treatment arms. Conclusions: NACT + IDS was associated with shorter and less complex surgeries in selected patients, but survival outcomes appeared similar when R0 was achieved. Data suggest that selective use of NACT in patients with extensive disease burden or limited general health status may be suitable, while confirming that complete cytoreduction remains the most critical prognostic factor, although these survival comparisons are exploratory given the retrospective design and limited sample size.

Activity of Potassium Channels in CD8+ T Lymphocytes: Diagnostic and Prognostic Biomarker in Ovarian Cancer?

CD8+ T cells play a role in the suppression of tumor growth and immunotherapy. Ion channels control the Ca2+-dependent function of CD8+ lymphocytes such as cytokine/granzyme production and tumor killing. Kv1.3 and KCa3.1 K+ channels stabilize the negative membrane potential of T cells to maintain Ca2+ influx through CRAC channels. We assessed the expression of Kv1.3, KCa3.1 and CRAC in CD8+ cells from ovarian cancer (OC) patients (n = 7). We found that the expression level of Kv1.3 was higher in patients with malignant tumors than in control or benign tumor groups while the KCa3.1 activity was lower in the malignant tumor group as compared to the others. We demonstrated that the Ca2+ response in malignant tumor patients is higher compared to control groups. We propose that altered Kv1.3 and KCa3.1 expression in CD8+ cells in OC could be a reporter and may serve as a biomarker in diagnostics and that increased Ca2+ response through CRAC may contribute to the impaired CD8+ function.

Decoding the Molecular Landscape of 262 Uterine Sarcomas: RNA-Seq Clustering of ESS, UTROSCT, and UUS with Prognostic Insights.

Low-grade endometrial stromal sarcomas (LG-ESS), high-grade ESS (HG-ESS), undifferentiated uterine sarcomas (UUS), and uterine tumors resembling ovarian sex cord tumors are distinct non-smooth muscle cell neoplasms with varying clinical outcomes, often exhibiting overlapping characteristics. Diagnosis can be supported by identifying characteristic recurrent translocations, which may be absent in some cases, complicating the distinction of equivocal cases. Additionally, cases with overlapping features of low-grade and high-grade characteristics are recognized. To address these challenges, we analyzed RNA-seq profiles of 262 cases. Our results revealed that LG-ESS, with and without recurrent fusions, clustered into 2 partially overlapping expression profiles associated with distinct overall and relapse-free survival outcomes, with the cluster containing a majority of fusion-negative tumors demonstrating better prognoses. uterine tumors resembling ovarian sex cord tumors expression profiles closely resembled those of both LG-ESS subgroups, with NCOA3 fusion-positive cases clustering in groups with better survival outcomes. Furthermore, a distinct cluster for HG-ESS with BCOR and YWHAE fusions was identified, differentiating these tumors from HG-ESS without fusions. ONECUT3 emerged as a potential specific marker for this HG-ESS-fusion entity. A significant expression overlap was observed between monomorphic HG-ESS without fusions and pleomorphic UUS. These samples separated further into 2 mixed clusters distinguished by differences in immune activity, which significantly influenced overall survival and relapse-free survival outcomes. Unsupervised clustering of UUS revealed subgroups resembling either HG-ESS or muscle-cell-differentiated tumors, suggesting that UUS may include poorly differentiated distinct entities, such as leiomyosarcoma, and that the distinction from HG-ESS may, in some cases, be arbitrary. Our transcriptome analysis highlights several entities with distinct survival characteristics, providing a foundation for further characterization of these rare, often difficult-to-classify, tumors.